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The limitation of traditional bone grafts could be overcome by applying engineered bone constructs, which are mainly produced by seeding suitable stem cells on appropriate scaffolds. So far, bone marrow-derived stromal cells have been the most applied cells in bone tissue engineering, but current data show that unrestricted somatic stem cells (USSCs) from human cord blood might actually be a better stem cell source due to the accessibility and noninvasive procedure of collection. In this study, we cultured USSCs on a plasma-treated electrospun polylactic-co-glycolic acid (PLGA) scaffold coated with nanohydroxyapatite (nHA). Adhesion and proliferation of USSCs on PLGA/nHA were assessed by scanning electron microscopy and MTT assay. Osteogenic differentiation of USSCs into osteoblast lineage cells was evaluated via alkaline phosphatase (ALP) activity and real-time polymerase chain reaction. Our observation showed that USSCs attached and proliferated on PLGA/nHA. Osteogenic differentiation was confirmed by increased ALP activity and OSTEONECTIN expression in USSCs on PLGA/nHA after the 1st week of the osteogenic period. Therefore, using USSCs on electrospun PLGA/nHA is a promising approach in bone tissue engineering.